Decreasing the incidence of post-operative AF, and hence the morbidity and mortality of high-risk CABG patients, could be more fruitfully approached by targeting the upstream combined processes of inflammation and coagulation activation induced by the surgical insult and associated ischemia-reperfusion (I/R). During CPB, the heart is subjected to ischemic periods of varying duration. The cardiac tissue at that point is electrically resting and its metabolic demands are accordingly low. However, there is also a severely diminished supply of oxygen and nutrients. This results in slow but direct myocardium cellular damage, which increases as ischemia duration increases. However, after reperfusion with oxygenated blood, oxidative stress actually peaks because of accumulated oxidative substrates and cellular depletion of reductive compounds. Cardiac damage related to ischemia-reperfusion will be exacerbated in the presence of co-morbidities, such as diabetes and CAD, which are pathologies with a significant reactive oxygen species (ROS) injury component. High levels of ROS in the myocardium contribute to both electrical and structural remodeling of the cardiac muscle, resulting in the development of AF.